The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 17(8), P. 807 - 821

Published: July 1, 2020

Abstract Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types immunotherapy, including adoptive cell transfer (ACT) immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, only subsets patients can benefit from them. Immune infiltrates in microenvironment (TME) been shown to play a key role development will affect outcomes patients. Comprehensive profiling tumor-infiltrating cells would shed light on mechanisms cancer–immune evasion, thus providing opportunities for novel therapeutic strategies. However, highly heterogeneous dynamic nature TME impedes precise dissection intratumoral cells. With recent advances single-cell technologies such as RNA sequencing (scRNA-seq) mass cytometry, systematic interrogation is feasible provide insights into functional diversities In this review, we outline progress particularly by focusing landmark studies characterization tumor-associated cells, summarize phenotypic connections with immunotherapy. We believe review could strengthen our understanding facilitate elucidation modulation progression, guide immunotherapies treatment.

Language: Английский

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Lactate in the Regulation of Tumor Microenvironment and Therapeutic Approaches

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: Nov. 1, 2019

Tumor cells must generate sufficient ATP and biosynthetic precursors in order to maintain cell proliferation requirements. Otto Warburg showed that tumor uptake high amounts of glucose producing large volumes lactate even the presence oxygen, this process is known as "Warburg effect or aerobic glycolysis". As a consequence such there an acidification extracellular pH microenvironment, ranging between 6.0-6.5. This acidosis favors processes metastasis, angiogenesis more importantly, immunosuppression, which has been associated worse clinical prognosis. Thus, should be thought important oncometabolite metabolic reprogramming cancer. In review, we summarized role regulating microenvironment cancer discuss its relevance up-regulation enzymes dehydrogenase (LDH) monocarboxilate transporters (MCTs) tumors. The goal review expose not only secondary product cellular waste cells, but also key molecule involved carcinogenesis well immune evasion. Finally, possible targeting production treatment discussed.

Language: Английский

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Lipids in the tumor microenvironment: From cancer progression to treatment

Progress in Lipid Research, Journal Year: 2020, Volume and Issue: 80, P. 101055 - 101055

Published: Aug. 11, 2020

Language: Английский

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Redox regulation of the immune response

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(10), P. 1079 - 1101

Published: Sept. 2, 2022

Abstract The immune-inflammatory response is associated with increased nitro-oxidative stress. aim of this mechanistic review to examine: (a) the role redox-sensitive transcription factors and enzymes, ROS/RNS production, activity cellular antioxidants in activation performance macrophages, dendritic cells, neutrophils, T-cells, B-cells, natural killer cells; (b) involvement high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), paraoxonase-1 (PON1), oxidized phospholipids regulating immune response; (c) detrimental effects hypernitrosylation chronic stress on response. redox changes during responses are orchestrated by actions nuclear factor-κB, HIF1α, target rapamycin, phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinases, 5' AMP-activated kinase, peroxisome proliferator-activated receptor. survival individual cells under control depends intracellular extracellular levels ROS/RNS. They heavily influenced including glutathione thioredoxin systems, factor erythroid 2-related 2, HDL/ApoA1/PON1 complex. Chronic inhibit those antioxidant tricarboxylic acid cycle, mitochondrial functions, metabolism cells. In conclusion, redox-associated mechanisms modulate metabolic reprogramming macrophage T helper cell polarization, phagocytosis, production pro- versus anti-inflammatory cytokines, training tolerance, chemotaxis, pathogen sensing, antiviral antibacterial effects, Toll-like receptor activity, endotoxin tolerance.

Language: Английский

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Hydrogen sulfide: An endogenous regulator of the immune system

Pharmacological Research, Journal Year: 2020, Volume and Issue: 161, P. 105119 - 105119

Published: Aug. 8, 2020

Hydrogen sulfide (H2S) is now recognized as an endogenous signaling gasotransmitter in mammals. It produced by mammalian cells and tissues various enzymes - predominantly cystathionine β-synthase (CBS), γ-lyase (CSE) 3-mercaptopyruvate sulfurtransferase (3-MST) but part of the H2S intestinal microbiota (colonic H2S-producing bacteria). Here we summarize available information on production functional role cell types typically associated with innate immunity (neutrophils, macrophages, dendritic cells, natural killer mast basophils, eosinophils) adaptive (T B lymphocytes) under normal conditions it relates to development inflammatory immune diseases. Special attention paid physiological pathophysiological aspects oral cavity colon, where parenchymal are exposed a special "H2S environment" due bacterial production. has many cellular molecular targets. Immune "surrounded" "cloud" H2S, result exogenous from surrounding which, turn, importantly regulates their viability function. Downregulation producing diseases, or genetic defects biosynthetic enzyme systems either lead spontaneous autoimmune disease accelerate onset worsen severity immune-mediated diseases (e.g. rheumatoid arthritis asthma). Low, regulated amounts when therapeutically delivered small molecule donors, improve function protect them against dysfunction induced noxious stimuli reactive oxygen species oxidized LDL). These effects contribute maintenance functions, can stimulate antimicrobial defenses exert anti-inflammatory therapeutic

Language: Английский

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Hair follicle immune privilege and its collapse in alopecia areata

Experimental Dermatology, Journal Year: 2020, Volume and Issue: 29(8), P. 703 - 725

Published: July 18, 2020

Anagen stage hair follicles (HFs) exhibit "immune privilege (IP)" from the level of bulge downwards to bulb. Both passive and active IP mechanisms protect HFs physiologically undesired immune responses limit surveillance. is relative, not absolute, primarily based on absent, or greatly reduced, intra-follicular antigen presentation via MHC class I II molecules, along with prominent expression "no danger" signals like CD200 creation an immunoinhibitory signalling milieu generated by secretory activities HFs. Perifollicular mast cells, Tregs other immunocytes may also contribute HF maintenance in healthy human skin. Collapse anagen bulb essential prerequisite for development alopecia areata (AA). In AA, lesional are rapidly infiltrated NKG2D + T cells natural killer (NK) while perifollicular acquire a profoundly pro-inflammatory phenotype interact autoreactive CD8+ cells. Using animal models, significant functional evidence has accumulated that demonstrates dominance system AA pathogenesis. Purified CD8+T-cell NK cell populations alone, which secrete fγ, suffice induce phenotype, CD4+T-cells aggravate it, iNKT provide relative protection against development. While collapse be induced exogenous agents, inherent deficiencies might confer increased susceptibility some individuals. Thus, key goal effective management re-establishment IP, will superior disease relapse.

Language: Английский

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Natural killer group 2D receptor and its ligands in cancer immune escape

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Feb. 27, 2019

The immune system plays important roles in tumor development. According to the immune-editing theory, escape is key survival, and exploring mechanisms of can provide a new basis for treatment tumors. In this review, we describe natural killer group 2D (NKG2D) receptor NKG2D ligand (NKG2DL) responses. Natural (NK) cells are cytotoxic system, activated on NK cell surface bind NKG2DL expressed cells, enabling activate kill cells. However, tumors clearance mediated by receptor/NKG2DL through various mechanisms. expression be regulated molecules, hypoxia microenvironment. Tumor regulate at level transcription, translation, post-translation thereby recognition particular, viruses hormones have special affect NKG2DL. Therefore, NKG2D\NKG2DL may applications as targets more effective antitumor therapy.

Language: Английский

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Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 772 - 784

Published: Jan. 18, 2024

Abstract There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 interleukin-15 (CAR19/IL-15) in 37 patients with CD19 + B malignancies. The primary objectives were safety efficacy, defined as day 30 overall response (OR). Secondary included 100 response, progression-free survival, survival CAR19/IL-15 NK persistence. No notable toxicities such cytokine release syndrome, neurotoxicity or graft-versus-host disease observed. OR rates 48.6% both. 1-year 68% 32%, respectively. Patients who achieved had higher levels longer persistence CAR-NK cells. Receiving from blood unit (CBU) nucleated red ≤ 8 × 10 7 collection-to-cryopreservation time 24 h was the most significant predictor superior outcome. these optimal CBUs highly functional enriched effector-related genes. In contrast, suboptimal upregulation inflammation, hypoxia cellular stress programs. Finally, using multiple mouse models, we confirmed antitumor activity CAR/IL-15 vivo. These findings uncover new features biology underscore importance donor selection therapies. ClinicalTrials.gov identifier: NCT03056339 .

Language: Английский

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Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

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The emerging field of oncolytic virus-based cancer immunotherapy

Trends in cancer, Journal Year: 2022, Volume and Issue: 9(2), P. 122 - 139

Published: Nov. 17, 2022

Language: Английский

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